Cellular Toxicity and Immunological Effects of Carbon-based Nanomaterials

Abstract

Background: Carbon nanomaterials are a growing family of materials featuring unique physicochemical properties, and their widespread application is accompanied by increasing human exposure.

Main body: Considerable efforts have been made to characterize the potential toxicity of carbon nanomaterials in vitro and in vivo. Many studies have reported various toxicology profiles of carbon nanomaterials. The different results of the cytotoxicity of the carbon-based materials might be related to the differences in the physicochemical properties or structures of carbon nanomaterials, types of target cells and methods of particle dispersion, etc. The reported cytotoxicity effects mainly included reactive oxygen species generation, DNA damage, lysosomal damage, mitochondrial dysfunction and eventual cell death via apoptosis or necrosis. Despite the cellular toxicity, the immunological effects of the carbon-based nanomaterials, such as the pulmonary macrophage activation and inflammation induced by carbon nanomaterials, have been thoroughly studied. The roles of carbon nanomaterials in activating different immune cells or inducing immunosuppression have also been addressed.

Conclusion: Here, we provide a review of the latest research findings on the toxicological profiles of carbon-based nanomaterials, highlighting both the cellular toxicities and immunological effects of carbon nanomaterials. This review provides information on the overall status, trends, and research needs for toxicological studies of carbon nanomaterials.

Keywords: Carbon nanomaterial; Cytotoxicity; Immunological effects; Macrophage.

Fig. 1

Various carbon-based nanomaterials were reported to induce cytotoxicity. Carbon nanotubes (CNTs) are thin carbon filaments with cylindrical structure that comprise single or multiple graphene sheets, termed as single-wall carbon nanotubes (SWCNTs) and multiwall carbon nanotubes (MWCNTs), respectively. C-fullerene is a carbon allotrope organized solely by 60 carbon atoms with a polygonal structure. Carbon black nanoparticle is a traditional nanosized carbon-based nanomaterial of diameter between 10 to 100 nm with three nanometric dimensions. Nanographite, also called graphite nanoplatelet, is a one-atom-thick and two-dimensional sheet of sp2-bonded carbon atoms. Single-walled carbon nanohorns (SWCNHs) are horn-shaped single-walled tubules with cone angles of approximately 20°

Fig. 2

The mechanisms by which carbon-based nanoparticles induce cytotoxicity of macrophages. Exposure of macrophages to carbon nanomaterials triggers a cascade of cellular and molecular events, such as ROS generation and lysosome damage, which serve as the mechanisms underlying carbon nanomaterial-induced cell death, including necrosis, apoptosis and pyroptosis. Carbon nanomaterials cause the mitochondrial dependent apoptotic cascades through ROS-activated MAPKs pathway. ROS could activate several transcription factors, such as NF-κB that regulates the inflammatory response. Carbon nanomaterials induce lysosomal membrane permeabilization (LMP), resulting in the translocation of cathepsins to the cytoplasm. ROS and LMP were reciprocal causation generating an amplification loop. LMP could potentially cause autophagy dysfunction. And inflammasome-dependent pyroptosis was initiated characterized by cleavage of caspase 1 and downstream IL-1β release

Fig. 3

MyD88 played a critical role in alveolar macrophage-mediated inflammatory response to CNTs. MyD88 mediated CNTs toxicity by linking IL-1R or TLR-dependent signaling and acted on downstream IRAKs and TRAFs, thus inducing proinflammatory NF-κB pathway. Also, MAPKs was involved in toxic response and MAPK inhibitors for p38 and JNK reduced levels of TNF-α and IL-1β. MyD88-specific inhibitory peptide blocked the production of TNF-α and IL-1β

Fig. 4

SWCNTs induced lung injury. Inhalation of SWCNTs could up-regulate chemokines, proteinases and several macrophage receptors, also resulting in NF-κB-related inflammatory responses, which play roles in lung pathology including airway hyperreaction, airflow obstruction and granuloma. In vitro experiments indicated that the cell-cell interaction of bronchoalveolar macrophages with lung epithelial cells induced MMP12 and cathepsin K. Blocking NF-κB with PDTC could attenuate SWCNTs-induced chemokine and proteinase expression